Endogenous opioid peptides (EOP; leucine5-enkephalin; methionine5-enkephalin, Beta-endorphin) and angiotensin II (ANG II) are neuroendocrine hormones postulated to function as neuromodulators and/or neurotransmitters within the central nervous system. EOP and ANG II are present in neuronal cell bodies and in nerve terminals localized in brain regions. Specific high affinity receptors for these peptides are also present in brain tissue. Neuropharmacological studies suggest ANG II regulates blood pressure and hydration by action on the central nervous syytem (CNS). Intracerebroventricular (IVT) administration of ANG II results in: 1) an elevation in blood pressure, 2) release of vasopressin from the neurohypophysis and 3) drinking behavior. Preliminary data demonstrate that intracerebroventricular (IVT) administration of enkephalin inhibits these CNS effects of ANG II by a naloxone-sensitive mechanism. Moreover, naloxone potentiates the pressor response to ANG II, IVT. Biochemical and anatomical studies also support an interaction of these two hormonal systems. Enzymes which are required for ANG II biosynthesis metabolize enkephalins (converting enzyme) and Beta-endorphin (renin). Enkephalin containing nerve endings are localized in brain regions having a high concentration of ANG II-containing terminals. EOP are also found in areas known to regulate blood pressure and hydration. To investigate the biological significance of an interaction of EOP with ANG II the proposed research will: 1) define the pharmacology of EOP inhibition of ANG II-stimulated pressor response, drinking behavior and vasopressin secretion, and 2) determine EOP effects in spontaneously hypertensive rats. ANG II maintains hypertension in these animals and contributes to essential hypertension in humans. The proposed research would clarify an interaction of EOP with ANG II in the regulation of blood pressure and hydration in normotensive and hypertenive rats. The pharmacology of these peptides and how they interact in the CNS will contribute basic knowledge concerning the neuroendocrinology of hydration and may define a potential pathophysiological role of these hormonal systems in hypertension.